Shouhui Tongbian capsule promotes calcium absorption by regulating gut microbiota and protects against osteoporosis.

BACKGROUND

Postmenopausal osteoporosis (OP) is a global health problem whose occurrence is strongly associated with intestinal flora dysbiosis. Shouhui Tongbian Capsule (SH) regulates gut microbiota for constipation/obesity, but its role, ability to counter calcium's side effects, and OP-related mechanism remain unclear.

PURPOSE: This study aimed to investigate the therapeutic effect of SH on OP and elucidate its mechanism in improving bone metabolism via gut microbiota regulation.

METHODS

Ovariectomized (OVX) mice received SH and/or calcium supplements. Gut microbiota profiles were analyzed via 16S rRNA sequencing, and functional annotations were performed using the Kyoto Encyclopedia of Genes and Genomes database. Gut barrier function was assessed through histology, tight junction protein expression, and serum biomarkers. Micro-CT was used to quantify the bone microstructure. Fecal microbiota transplantation (FMT) validated the microbiota-dependent effects. Osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) was assessed by calcium deposition staining and western blotting.

RESULTS

SH restored gut barrier integrity, reduced systemic inflammation, and alleviated constipation. SH reshaped the gut microbiota composition, enriched Lactobacillus, Lachnospiraceae, and Akkermansia, and strengthened metabolic pathways related to mineral absorption. SH synergized with calcium supplementation to significantly enhance bone mass in OVX mice. FMT experiments recapitulated the osteoprotective effects of SH, with calcium supplementation being a necessary factor in this process. SH potentiated the osteogenic capacity of BMSCs while having no effect on osteoclast differentiation.

CONCLUSION

SH ameliorates OP via the "microbiota-mineral absorption-osteogenesis" network by alleviating calcium-induced intestinal dysbiosis and promoting bone formation. This study is the first to confirm SH's synergistic regulation of gut microbiota and calcium metabolism against OP, offering novel insights for gut-bone axis-based OP therapies and highlighting traditional Chinese medicine's innovative potential in metabolic bone diseases.